Jeroen Vos

Sirolimus-eluting stent for treatment of complex in-stent restenosis: the first clinical experience.

OBJECTIVES In this study, we assess the value of sirolimus eluting stent (SES) implantation in patients with complex in-stent restenosis (ISR). BACKGROUND The treatment of ISR remains a therapeutic challenge, since many pharmacological and mechanical approaches have shown disappointing results. The SESs have been reported to be effective in de-novo coronary lesions. METHODS Sixteen patients with severe, recurrent ISR in a native coronary artery (average lesion length 18.4 mm) and objective evidence of ischemia were included. They received one or more 18 mm Bx VELOCITY SESs (Cordis Waterloo, Belgium). Quantitative angiographic and three-dimensional intravascular ultrasound (IVUS) follow-up was performed at four months, and clinical follow-up at nine months. RESULTS The SES implantation (n = 26) was successful in all 16 patients. Four patients had recurrent restenosis following brachytherapy, and three patients had totally occluded vessels preprocedure. At four months follow-up, one patient had died and three patients had angiographic evidence of restenosis (one in-stent and two in-lesion). In-stent late lumen loss averaged 0.21 mm and the volume obstruction of the stent by IVUS was 1.1%. At nine months clinical follow-up, three patients had experienced four major adverse cardiac events (two deaths and one acute myocardial infarction necessitating repeat target vessel angioplasty). CONCLUSIONS The SES implantation in patients with severe ISR lesions effectively prevents neointima formation and recurrent restenosis at four months angiographic follow-up.

Non-invasive coronary angiography with multislice spiral computed tomography: impact of heart rate

Objective: To evaluate the impact of heart rate on the diagnostic accuracy of coronary angiography by multislice spiral computed tomography (MSCT). Design: Prospective observational study. Patients: 78 patients who underwent both conventional and MSCT coronary angiography for suspicion of de novo coronary artery disease (n=53) or recurrent coronary artery disease after percutaneous intervention (n=25). Setting: Tertiary referral centre. Methods: Intravenously contrast enhanced MSCT coronary angiography was done during a single breath hold, and ECG synchronised images were reconstructed retrospectively. All coronary segments of ≥ 2.0 mm without stents were evaluated by two investigators and compared with quantitative coronary angiography. Patients were classified according to the average heart rate (mean (SD)) into three equally sized groups: group 1, 55.8 (4.1) beats/min; group 2, 66.6 (2.8) beats/min; group 3, 81.7 (8.8) beats/min. Results: Image quality was sufficient for analysis in 78% of the coronary segments in patients in group 1, 73% in group 2, and 54% in group 3 (p < 0.01). The sensitivity and specificity for detecting significant stenoses (≥ 50% lumen reduction) in these assessable segments were: 97% (95% confidence interval (CI) 84% to 100%) and 96% in group 1; 74% (52% to 89%) and 94% in group 2; and 67% (33% to 90%) and 94% in group 3 (p < 0.05). Accounting for all segments of ≥ 2.0 mm, including lesions in non-assessable segments as false negatives, the sensitivity decreased to 82% (28/34 lesions, 95% CI 69% to 91%), 61% (14/23 lesions, 42% to 77%), and 32% (6/19 lesions, 15% to 50%), respectively (p < 0.01). Conclusions: MSCT allows reliable coronary angiography in patients with low heart rates.

Persistent inhibition of neointimal hyperplasia after sirolimus-eluting stent implantation: long-term (up to 2 years) clinical, angiographic, and intravascular ultrasound follow-up

Background—Early results of sirolimus-eluting stent implantation showed a nearly complete abolition of neointimal hyperplasia. The question remains, however, whether the early promising results will still be evident at long-term follow-up. The objective of our study was to evaluate the efficiency of sirolimus-eluting stent implantation for up to 2 years of follow-up. Methods and Results—Fifteen patients with de novo coronary artery disease were treated with 18-mm sirolimus-eluting Bx-Velocity stents (Cordis) loaded with 140 &mgr;g sirolimus/cm2 metal surface area in a slow release formulation. Quantitative angiography (QCA) and intravascular ultrasound (IVUS) were performed according to standard protocol. Sirolimus-eluting stent implantation was successful in all 15 patients. During the in-hospital course, 1 patient died of cerebral hemorrhage after periprocedural administration of abciximab, and 1 patient underwent repeat stenting after 2 hours because of edge dissection that led to acute occlusion. Through 6 months and up to 2 years of follow-up, no additional events occurred. QCA analysis revealed no significant change in stent minimal lumen diameter or percent diameter stenosis, and 3-dimensional IVUS showed no significant deterioration in lumen volume. In 2 patients, additional stenting was performed because of significant lesion progression remote from the sirolimus-eluting stent. Conclusion—Sirolimus-eluting stents showed persistent inhibition of neointimal hyperplasia for up to 2 years of follow-up.

Prevention of Restenosis After Percutaneous Transluminal Coronary Angioplasty With Thromboxane A2-receptor Blockade - a Randomized, Double-blind, Placebo-controlled Trial

BackgroundGR32191B is a novel thromboxane A2-receptor antagonist with potent antiaggregational and antivasoconstrictive properties. We have conducted a randomized, doubleblind, placebo-controlled trial to study its usefulness in restenosis prevention. Methods and ResultsPatients received either GR32191B (80 mg orally before angioplasty and 80 mg/day orally for 6 months) or 250 mg i.v. aspirin before angioplasty and placebo fo6 months. Coronary angiograms before angioplasty, after angioplasty, and at 6-month follow-up were quantitatively analyzed. Angioplasty was attempted in 697 patients. For efficacy analysis, quantitative angiography at follow-up was available in 522 compliant patients (261 in each group). Baseline clinical and angiographic parameters did not differ between the two treatment groups. The mean difference in coronary diameter between postangioplasty and follow-up angiogram (primary end point) was −0.31 + 0.54 mm in the control group and −0.31 + 0.55 mm in the GR32191B group. Clinical events during 6-month follow-up, analyzed on intention-totreat basis, were ranked according to the highest category on a scale ranging from death (control, six; GR32191B, four) to nonfatal infarction (control, 22; GR32191B, 18), bypass grafting (control, 19; GR32191B, 22) and repeat angioplasty (control, 52; GR32191B, 48). No significant difference in ranking was detected. Six months after angioplasty, 75% of patients in the GR32191B group and 72% of patients in the control group were symptom free. ConclusionsLong-term thromboxane A2-receptor blockade with GR32191B does not prevent restenosis and does not favorably influence the clinical course after angioplasty.

Long-term benefit of early thrombolytic therapy in patients with acute myocardial infarction: 5 year follow-up of a trial conducted by the Interuniversity Cardiology Institute of the Netherlands

Patients (n = 533) who participated in the Interuniversity Cardiology Institute of the Netherlands Trial were followed up for 3 to 7 years. The 5 year survival rate after thrombolytic therapy with intracoronary streptokinase was 81% (269 patients) compared with 71% after conventional therapy (264 patients). The greatest improvement in survival was observed in patients with anterior infarction (81% versus 64% with thrombolytic therapy or conventional therapy, respectively), in those with heart failure on admission or a previous infarction and in those with extensive myocardial ischemia on admission. Left ventricular ejection fraction at the time of hospital discharge was better after thrombolytic therapy. In the hospital survivors, long-term outcome was related to left ventricular function at the time of discharge and, to a lesser extent, to the underlying coronary artery disease. The initial therapy (thrombolysis or conventional) was not an independent additional determinant of long-term survival when left ventricular function and coronary status at the time of hospital discharge were taken into account. Thus, the salutary effects of thrombolytic therapy appear to be the result of myocardial salvage. Reinfarction within 3 years was observed more frequently after thrombolytic therapy, particularly in patients with inferior wall infarction and those with greater than or equal to 90% stenosis of the infarct-related vessel at discharge. Coronary bypass surgery and coronary angioplasty were performed more frequently after thrombolytic therapy than in conventionally treated patients. At 5 years, approximately 40% of patients in both groups had an uneventful course without reinfarction or additional revascularization procedures. These observations demonstrate that the benefits of thrombolytic therapy are maintained throughout 5 years of follow-up.(ABSTRACT TRUNCATED AT 250 WORDS)

SeminarAcute myocardial infarction

Acute myocardial infarction is a common disease with serious consequences in mortality, morbidity, and cost to the society. Coronary atherosclerosis plays a pivotal part as the underlying substrate in many patients. In addition, a new definition of myocardial infarction has recently been introduced that has major implications from the epidemiological, societal, and patient points of view. The advent of coronary-care units and the results of randomised clinical trials on reperfusion therapy, lytic or percutaneous coronary intervention, and chronic medical treatment with various pharmacological agents have substantially changed the therapeutic approach, decreased in-hospital mortality, and improved the long-term outlook in survivors of the acute phase. New treatments will continue to emerge, but the greatest challenge will be to effectively implement preventive actions in all high-risk individuals and to expand delivery of acute treatment in a timely fashion for all eligible patients.

Pharmacological approaches to the prevention of restenosis following angioplasty. The search for the Holy Grail? (part II)

SummaryLuminal renarrowing after balloon angioplasty still hampers the long term vessel patency in a substantial percentage of patients. Morphologically, the restenotic lesion comprises hyperplasia of intimai tissue, which is mainly characterised by proliferation of smooth muscle cells of the synthetic type with abundant extracellular matrix production, chiefly composed of proteoglycans. Unravelling the underlying pathophysiological process enables more specific intervention in basic interactions and cell responses. Critical events in the development of restenotic tissue are platelet aggregation and thrombus formation, while the release of several mediators promotes proliferation and migration of various cell types. All of these steps give access for a diversity of pharmacological interventions. With this in mind, antithrombotic, antiplatelet, antiproliferative, antiinflammatory, calcium channel blocking and lipid-lowering drugs have been investigated in the prevention of restenosis.Part II of this article reviews newer approaches, such as antibodies to growth factors, gene transfer and antisense oligonucleotides.

Extension of Increased Atherosclerotic Wall Thickness Into High Shear Stress Regions Is Associated With Loss of Compensatory Remodeling

Background Atherosclerosis preferentially develops at average low shear stress (SS) locations. SS‐related signaling maintains lumen dimensions by inducing outward arterial remodeling. Prolonged plaque accumulation at low SS predilection locations explains an inverse relation between wall thickness (WT) and SS. No data exist on WT‐SS relations when lumen narrowing and loss of compensatory remodeling commence. Methods and Results In 14 patients, an angiographically normal artery (stenosis <50%) was investigated with ANGiography and ivUS (ANGUS) to provide 3D lumen and wall geometry. Selection of segments >5 mm in length, in between side branches, yielded 25 segments in 12 patients. SS at the wall was calculated by computational fluid dynamics. WT smaller than 0.2*lumen diameter was defined as normal. Largest arc of normal WT defined reference cross sections. Lumen area relative to the reference cross sections defined area stenosis (AS). Average segmental AS smaller or greater than 10% defined preserved or narrowed lumen, respectively. Total vessel area relative to the reference defined vascular remodeling (VR). For the preserved lumens (n=11, AS=1.7±5.6%, P=NS), axially averaged WT and SS were inversely related (slope, ‐0.46±0.55 mm/Pa, P<0.05) and VR was positive (7±9%, P<0.05). Narrowed segments (n=13, 1 excluded, AS=18±6%, P<0.05) showed no relation between WT and SS or vascular remodeling. Conclusions In patient coronary arteries, the often‐reported inverse WT‐SS relationship appears restricted to lumen preservation and positive vascular remodeling. Its disappearance with lumen narrowing suggests a growing importance of non‐SS‐related plaque progression. (Circulation. 2003;108:17‐23.)

Luminal narrowing after percutaneous transluminal coronary angioplasty. A study of clinical, procedural, and lesional factors related to long-term angiographic outcome. Coronary Artery Restenosis Prevention on Repeated Thromboxane Antagonism (CARPORT) Study Group.

BACKGROUND The renarrowing process after successful percutaneous transluminal coronary angioplasty (PTCA) is now believed to be caused by a response-to-injury vessel wall reaction. The magnitude of this process can be assessed by the change in minimal lumen diameter (MLD) at follow-up angiography. The aim of the present study was to find independent patient-related, lesion-related, and procedure-related risk factors for this luminal narrowing process. A model that accurately predicts the amount of luminal narrowing could be an aid in patient or lesion selection for the procedure, and it could improve assessment of medium-term (6 months) prognosis. Modification or control of the identified risk factors could reduce overall restenosis rates, and it could assist in the selection of patients at risk for a large loss in lumen diameter. This population could then constitute the target population for pharmacological intervention studies. METHODS AND RESULTS Quantitative angiography was performed on 666 successfully dilated lesions at angioplasty and at 6-month follow-up. Multivariate linear regression analysis was performed to obtain variables with an independent contribution to the prediction of the absolute change in minimal lumen diameter. Diabetes mellitus, duration of angina < 2.3 months, gain in MLD at angioplasty, pre-PTCA MLD, lesion length > or = 6.8 mm, and thrombus after PTCA were independently predictive of change in MLD. Overall prediction of the model was poor, however, percentage-correct classification for a predicted change between -0.1 to -0.4 mm was approximately 10%. Lesions showing no change or regression (change > -0.1 mm) and lesions showing large progression (< or = -0.4 mm) were more predictable (correct classification, 59.5% and 49.7%, respectively). CONCLUSIONS Renarrowing after successful PTCA as determined with contrast angiography is a process that cannot be accurately predicted by simple clinical, morphological, and lesion characteristics.

A single dose of erythropoietin in ST-elevation myocardial infarction

AIMS Cardioprotective effects of erythropoietin (EPO) have been shown in experimental and smaller clinical studies. We performed a prospective, multicentre, randomized trial to assess the effects of a single high dose of EPO after primary coronary intervention (PCI) for an ST-elevation myocardial infarction (STEMI). Methods and results Patients with a successful PCI for a first STEMI were randomized to receive either standard medical care alone, or in combination with a single bolus with 60,000 IU i.v. of epoetin alfa within 3 h after PCI. Primary endpoint was left ventricular ejection fraction (LVEF) after 6 weeks, assessed by planar radionuclide ventriculography. Pre-specified secondary endpoints included enzymatic infarct size and major adverse cardiovascular events. A total of 529 patients were enrolled (EPO n = 263, control n = 266). At baseline (before EPO administration), groups were well-matched for all relevant characteristics. After a mean of 6.5 (± 2.0) weeks, LVEF was 0.53 (± 0.10) in the EPO group and 0.52 (± 0.11) in the control group (P = 0.41). Median area under the curve (inter-quartile range) after 72 h for creatinine kinase was 50 136 (28 212-76 664)U/L per 72 h in the EPO group and 53 510 (33 973-90 486)U/L per 72 h in the control group (P = 0.058). More major adverse cardiac events occurred in the control than in the EPO group (19 vs. 8; P = 0.032). Conclusion A single high dose of EPO after a successful PCI for a STEMI did not improve LVEF after 6 weeks. However, the use of EPO was related to less major adverse cardiovascular events and a favourable clinical safety profile. CLINICAL TRIAL REGISTRATION INFORMATION NCT00449488; http://www.clinicaltrials.gov/ct2/show/NCT00449488?term=voors&rank=2.